The molecular events of the general recombination processes for bacteriophage lambda DNA are likely to be chemically analogous to at least some of those accompanying the integration of tumor virus DNA into host cell genomes. The abundance of existing genetic, physiological, and biochemical information make lambda an ideal model system for studies of recombination at the molecular level. A prerequisite to such studies is a cell-free recombination system, in which the proteins and other cellular elements which catalyze recombination can be subjected to isolation, purification, and biochemical characterization, along with the DNA substrates for the component reactions. A unique biochemical DNA-joining assay for recombination, offering significant advantages over current techniques used to detect recombination, is proposed. Step-by-step development procedures based on preliminary experiments in this laboratory using the DNA-joining assay and other recombination assays, are described. The application of the cell-free systems to biochemical analyses of recombination pathways is outlined. An alternative approach to studies of general recombination systems, using intramolecular DNA substrates, is discussed as well. An obstacle to a truly molecular description of recombination is the lack of knowledge of the physical driving forces involved in the interactions of the recombining DNA molecules with one another and with other cellular components. Model DNA substrates, whose structure can be systematically varied (with respect to nicks, gaps, etc.), and whose interaction can be followed by the DNA-joining assay, will be used to study this problem.